Supplementation of Vitamin D and Mental Health in Adults with Respiratory System Diseases: A Systematic Review of Randomized Controlled Trials

Vitamin D is indicated to be beneficial for the prevention and treatment of both respiratory health and mental health problems, while mental health issues are a common consequence of diseases of the respiratory system. The aim of the presented systematic review was to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). The systematic review was conducted on the basis of the PubMed and Web of Science databases in agreement with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), while being registered within the database of the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020155779). A total of 8514 studies published before September 2021 were screened and 5 RCTs were included, which were assessed using the revised Cochrane risk-of-bias tool for randomized trials. Screening, inclusion, reporting, and assessment were conducted by two researchers independently. The studies focused on the assessment of patients with chronic obstructive pulmonary disease, but also increased susceptibility to respiratory tract infections, pulmonary tuberculosis, and bronchial asthma. The studies were conducted for various periods of time—from 2 months to a year—while the dose of vitamin D applied was also diverse—from 4000 IU applied daily, to 100,000 IU applied weekly, or monthly. The psychological measures applied within the studies allowed the assessment, mainly, of quality of life, but also well-being, and depression. For the majority of studies, some concerns regarding risk of bias were defined, resulting from the randomization process and selection of reported results; however, for one study, the risk was even defined as high. Within the included studies, three studies confirmed a beneficial effect of vitamin D (including those with a high risk of bias), but two studies did not confirm it. Taking into account the evidence gathered, in spite of a positive influence of vitamin D on mental health in individuals with increased susceptibility to respiratory tract infections and bronchial asthma, the conducted systematic review is not a strong confirmation of the beneficial effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases.


Introduction
The diseases of the respiratory system are a large group of various diseases with a diverse etiology, including infections, toxic agents, accidents, risky behaviors such as smoking, and genetic factors [1]. They are classified within the International Classification of Diseases (ICD-11), in the 12th chapter, but tuberculosis of the respiratory system, classified as well as inflammatory bowel diseases and irritable bowel syndrome [23]. However, respiratory system diseases are now the key focus for the gathered studies.

The Search Strategy and Eligibility Assessment
An electronic search was aimed at gathering RCTs regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases, based on the inclusion criteria listed: studied an adult population; -studied a population with any diagnosed respiratory system disease, based on ICD-11: all included in the 12th chapter, and tuberculosis of the respiratory system (1B10) [2]; -applied oral supplementation of a specified dose of vitamin D and compared with placebo; -any mental health outcome monitored within the study using a valid psychological measure (either subjective or objective); -study defined as RCT; -study available in a peer-reviewed journal. - The exclusion criteria were applied as listed: -animal model study; -influence of a combination of multiple nutrients presented; -studied a population of pregnant women; -studied a population of patients with concurrent eating disorders; -studied a population of patients with concurrent intellectual disabilities; -studied a population of patients with concurrent neurological disorders; -study not published in English.
The population, intervention/exposure, comparator, outcome, and study design (PICOS) criteria for the presented study are described in Table 1. Table 1. The population, intervention/exposure, comparator, outcome, and study design (PICOS) criteria.

PICOS Criterion Inclusion Exclusion
Population Adult patients with any respiratory system disease diagnosed  Once the eligible studies were included, they were analyzed to derive the data needed to describe the study and the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases. The general description of the study included: authors and year of publication, country and detailed location, general description of the studied population, as well as the period of study. The description of the studied population included the number, gender and age of participants, as well as inclusion and exclusion criteria. The description of the supplementation of vitamin D included the dosage regimen, intervention duration, and time of intervention, while the description of the assessment of mental health included an applied psychological measure. Once the eligible studies were included, they were analyzed to derive the data needed to describe the study and the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases. The general description of the study included: authors and year of publication, country and detailed location, general description of the studied population, as well as the period of study. The description of the studied population included the number, gender and age of participants, as well as inclusion and exclusion criteria. The description of the supplementation of vitamin D included the dosage regimen, intervention duration, and time of intervention, while the description of the assessment of mental health included an applied psychological measure. The description of the prominent observations and conclusions was based on those drawn up by authors.
If possible, all data were obtained from a published study. If this was not possible, other publications referred to within the study were addressed. If this was not possible, Nutrients 2023, 15, 971 5 of 12 the corresponding authors were contacted and asked for them. Two researchers independently extracted the data, but if any disagreement appeared, it was discussed with a third investigator until consensus was achieved.

The Quality of Studies and Risk-of-Bias Assessment
The quality of studies was determined based on a risk of bias defined for the studies [24]. The revised Cochrane risk-of-bias tool for randomized trials with the RoB 2 tool (7.0) [25] was applied for the assessment of the risk of bias, as it is the most frequently used for randomized trials [26].
The revised Cochrane risk-of-bias tool for randomized trials consists of an assessment of five distinct domains of the risk of bias: (1) arising from the randomization process; (2) due to deviations from the intended interventions; (3) due to missing outcome data; (4) in the measurement of the outcome; and (5) in the selection of the reported results. Afterwards, it was assessed for the overall risk [27]. The risk-of-bias assessment within the revised Cochrane risk-of-bias tool for randomized trials for each domain is formulated as: (1) low risk of bias; (2) some concerns; or (3) high risk of bias, while the final assessment is based on the summarized assessment [26].
Two researchers independently assessed the studies, but if any disagreement appeared, it was discussed with a third investigator until consensus was achieved.

Results
The general descriptions of the studies included in the systematic review [28][29][30][31][32] are presented in Table 2. The studies focused on the assessment of patients with chronic obstructive pulmonary disease (COPD) [28,31], but also increased susceptibility to respiratory tract infections [29], pulmonary tuberculosis [30], and bronchial asthma [32]. The majority of studies were conducted in European countries: Belgium [28], Sweden [29], and Spain [32], but also in China [30] and Iran [31]. The descriptions of the studied populations within the studies included in the systematic review are presented in Table 3. The studies were conducted mostly in quite large samples of more than 100 participants (studied group and placebo group combined), with various proportions of female and male participants [28][29][30]32], but one study was conducted in a medium-sized sample of fewer than 100 participants, with a very small share of women [31]. The studies were conducted in populations of middle-aged adults of various ages-from a population of individuals in their 30-40s [30], or a population of individuals in their 50s [28,32], to a population of individuals in their 60s [28,31]. The inclusion and exclusion criteria were developed based on the studied population (studied disease of the respiratory system), but with additional criteria in order to gather a sample with a major depressive disorder diagnosed [30], or vitamin D deficiency [31,32].  The descriptions of the supplementation of vitamin D, accompanied by the descriptions of the assessments of mental health within the studies included in the systematic review are presented in Table 4. The studies were conducted for various periods of time-2 months [30], 6 months [31,32], or a year [28,29]. The dose of vitamin D applied within the studies was also diverse-4000 IU applied daily [29], 16,000 IU applied weekly [32], 50,000 IU applied weekly or monthly [31], or 100,000 IU applied weekly [30] or monthly [28]. The psychological measures applied within the studies allowed the assessment, mainly, of quality of life [28,31,32], but also well-being [29], and depression [30]. The risk-of-bias assessments for studies, conducted using the revised Cochrane risk-ofbias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30]. The risk-of-bias assessments for studies, conducted using the revised Cochrane riskof-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30]. -Some concerns -High risk; * the summary of conclusions defined as confirming (if confirming a positive influence of vitamin D supplementation on mental health) or not confirming (if not confirming a positive influence of vitamin D supplementation on mental health); domains of risk of bias: D1-arising from the randomization process; D2-due to deviations from the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcome; D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and The risk-of-bias assessments for studies, conducted using the revised Cochrane ris of-bias tool for randomized trials, accompanied by the main results of the studies includ in the systematic review, are presented in Table 5. For the majority of studies, some co cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomizati process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. Ho ever, for one study [29], the risk was even defined as high. At the same time, it should indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect vitamin D (including those with a high risk of bias [29]), but two studies did not confir it [28,30]. -Some concerns -High risk; * the summary of conclusions defined as co firming (if confirming a positive influence of vitamin D supplementation on mental health) or n confirming (if not confirming a positive influence of vitamin D supplementation on mental healt domains of risk of bias: D1-arising from the randomization process; D2-due to deviations fro the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcom D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence the supplementation of vitamin D on mental health in adults with respiratory system d eases obtained within randomized controlled trials (RCTs). However, the results shou not be considered as a strong confirmation of a general positive effect of the suppleme tation of vitamin D on mental health in adults with respiratory system diseases, as t beneficial effect was observed for increased susceptibility to respiratory tract infectio [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], wh for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such beneficial effect was not observed. Not only should a general positive influence not concluded, but also a beneficial effect in specific conditions cannot be stated, as only sing RCTs confirming were gathered for each mentioned disease. However, an increased su ceptibility to respiratory tract infections, bronchial asthma and COPD may be indicat as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are sociated with the general influence of vitamin D, being associated with immune functio [15]. It is observed that it influences the immunity by triggering the induction of cathe cidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. the same time, vitamin D influences autophagy, as well as adaptive immune respons by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review a The risk-of-bias assessments for studies, conducted using the revised of-bias tool for randomized trials, accompanied by the main results of the s in the systematic review, are presented in Table 5. For the majority of stu cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the process [31,32], and from a risk of bias in selection of the reported results [ ever, for one study [29], the risk was even defined as high. At the same ti indicated that within the studies, three studies [29,31,32] confirmed the be vitamin D (including those with a high risk of bias [29]), but two studies it [28,30].

Discussion
This systematic review aimed to gather available evidence regarding the supplementation of vitamin D on mental health in adults with respira eases obtained within randomized controlled trials (RCTs). However, th not be considered as a strong confirmation of a general positive effect of tation of vitamin D on mental health in adults with respiratory system beneficial effect was observed for increased susceptibility to respiratory [29] and bronchial asthma [32], as well as for one study conducted for CO for the other study conducted for COPD [28], and for pulmonary tubercul beneficial effect was not observed. Not only should a general positive i concluded, but also a beneficial effect in specific conditions cannot be state RCTs confirming were gathered for each mentioned disease. However, a ceptibility to respiratory tract infections, bronchial asthma and COPD m as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract i sociated with the general influence of vitamin D, being associated with im [15]. It is observed that it influences the immunity by triggering the indu cidin, being an antimicrobial peptide capable of mediating antimicrobial the same time, vitamin D influences autophagy, as well as adaptive imm by promoting regulatory lymphocytes [34]. It was confirmed by the system The risk-of-bias assessments for studies, conducted usin of-bias tool for randomized trials, accompanied by the main r in the systematic review, are presented in Table 5. For the m cerns were defined [28,[30][31][32], resulting from a risk of bias ar process [31,32], and from a risk of bias in selection of the repo ever, for one study [29], the risk was even defined as high. A indicated that within the studies, three studies [29,31,32] con vitamin D (including those with a high risk of bias [29]), but it [28,30]. Table 5. The risk of bias assessments for studies, conducted using t tool for randomized trials, accompanied by the main results of the s review.

Ref
Overall Bias [28] [29] [30] [31] [32] -Low risk; -Some concerns -High risk; * the summar firming (if confirming a positive influence of vitamin D suppleme confirming (if not confirming a positive influence of vitamin D sup domains of risk of bias: D1-arising from the randomization proce the intended interventions; D3-due to missing outcome data; D4-D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available eviden the supplementation of vitamin D on mental health in adults eases obtained within randomized controlled trials (RCTs). not be considered as a strong confirmation of a general posi tation of vitamin D on mental health in adults with respira beneficial effect was observed for increased susceptibility t [29] and bronchial asthma [32], as well as for one study con for the other study conducted for COPD [28], and for pulmo beneficial effect was not observed. Not only should a gene concluded, but also a beneficial effect in specific conditions ca RCTs confirming were gathered for each mentioned disease ceptibility to respiratory tract infections, bronchial asthma a as a promising area to be studied in the future.
The effects observed for increased susceptibility to resp sociated with the general influence of vitamin D, being assoc [15]. It is observed that it influences the immunity by trigge cidin, being an antimicrobial peptide capable of mediating a the same time, vitamin D influences autophagy, as well as by promoting regulatory lymphocytes [34]. It was confirmed indicated that within the studies, three studies [ vitamin D (including those with a high risk of it [28,30]. [30] [31] [32] -Low risk; -Some concerns -High risk firming (if confirming a positive influence of vitami confirming (if not confirming a positive influence of domains of risk of bias: D1-arising from the rando the intended interventions; D3-due to missing outc D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather av the supplementation of vitamin D on mental he eases obtained within randomized controlled t not be considered as a strong confirmation of a tation of vitamin D on mental health in adult beneficial effect was observed for increased su [29] and bronchial asthma [32], as well as for o for the other study conducted for COPD [28], a beneficial effect was not observed. Not only s concluded, but also a beneficial effect in specific RCTs confirming were gathered for each menti ceptibility to respiratory tract infections, bronc as a promising area to be studied in the future.
The effects observed for increased suscept sociated with the general influence of vitamin D [15]. It is observed that it influences the immun cidin, being an antimicrobial peptide capable o the same time, vitamin D influences autophag by promoting regulatory lymphocytes [34]. It w indicated that within the studies, vitamin D (including those with it [28,30].

Discussion
This systematic review aime the supplementation of vitamin D eases obtained within randomize not be considered as a strong con tation of vitamin D on mental h beneficial effect was observed fo [29] and bronchial asthma [32], a for the other study conducted for beneficial effect was not observe concluded, but also a beneficial ef RCTs confirming were gathered ceptibility to respiratory tract inf as a promising area to be studied The effects observed for incr sociated with the general influenc [15]. It is observed that it influen cidin, being an antimicrobial pep the same time, vitamin D influen by promoting regulatory lympho Not confirming [29] The risk-of-bias assessments for studies, conducted using the revised Cochrane riskof-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30]. Table 5. The risk of bias assessments for studies, conducted using the revised Cochrane risk-of-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review. -Some concerns -High risk; * the summary of conclusions defined as confirming (if confirming a positive influence of vitamin D supplementation on mental health) or not confirming (if not confirming a positive influence of vitamin D supplementation on mental health); domains of risk of bias: D1-arising from the randomization process; D2-due to deviations from the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcome; D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and The risk-of-bias assessments for studies, conducted using the revised Cochrane ris of-bias tool for randomized trials, accompanied by the main results of the studies includ in the systematic review, are presented in Table 5. For the majority of studies, some co cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomizati process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. Ho ever, for one study [29], the risk was even defined as high. At the same time, it should indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect vitamin D (including those with a high risk of bias [29]), but two studies did not confir it [28,30]. Table 5. The risk of bias assessments for studies, conducted using the revised Cochrane risk-of-b tool for randomized trials, accompanied by the main results of the studies included in the systema review. -Some concerns -High risk; * the summary of conclusions defined as co firming (if confirming a positive influence of vitamin D supplementation on mental health) or n confirming (if not confirming a positive influence of vitamin D supplementation on mental healt domains of risk of bias: D1-arising from the randomization process; D2-due to deviations fro the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcom D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence the supplementation of vitamin D on mental health in adults with respiratory system d eases obtained within randomized controlled trials (RCTs). However, the results shou not be considered as a strong confirmation of a general positive effect of the suppleme tation of vitamin D on mental health in adults with respiratory system diseases, as t beneficial effect was observed for increased susceptibility to respiratory tract infectio [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], wh for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such beneficial effect was not observed. Not only should a general positive influence not concluded, but also a beneficial effect in specific conditions cannot be stated, as only sing RCTs confirming were gathered for each mentioned disease. However, an increased su ceptibility to respiratory tract infections, bronchial asthma and COPD may be indicat as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are sociated with the general influence of vitamin D, being associated with immune functio [15]. It is observed that it influences the immunity by triggering the induction of cathe cidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. the same time, vitamin D influences autophagy, as well as adaptive immune respons by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review a Nutrients 2023, 15, x FOR PEER REVIEW The risk-of-bias assessments for studies, conducted using the revised of-bias tool for randomized trials, accompanied by the main results of the s in the systematic review, are presented in Table 5. For the majority of stu cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the process [31,32], and from a risk of bias in selection of the reported results [ ever, for one study [29], the risk was even defined as high. At the same ti indicated that within the studies, three studies [29,31,32] confirmed the be vitamin D (including those with a high risk of bias [29]), but two studies it [28,30].

Discussion
This systematic review aimed to gather available evidence regarding the supplementation of vitamin D on mental health in adults with respira eases obtained within randomized controlled trials (RCTs). However, th not be considered as a strong confirmation of a general positive effect of tation of vitamin D on mental health in adults with respiratory system beneficial effect was observed for increased susceptibility to respiratory [29] and bronchial asthma [32], as well as for one study conducted for CO for the other study conducted for COPD [28], and for pulmonary tubercul beneficial effect was not observed. Not only should a general positive i concluded, but also a beneficial effect in specific conditions cannot be state RCTs confirming were gathered for each mentioned disease. However, a ceptibility to respiratory tract infections, bronchial asthma and COPD m as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract i sociated with the general influence of vitamin D, being associated with im [15]. It is observed that it influences the immunity by triggering the indu cidin, being an antimicrobial peptide capable of mediating antimicrobial the same time, vitamin D influences autophagy, as well as adaptive imm by promoting regulatory lymphocytes [34]. It was confirmed by the system Nutrients 2023, 15, x FOR PEER REVIEW The risk-of-bias assessments for studies, conducted usin of-bias tool for randomized trials, accompanied by the main r in the systematic review, are presented in Table 5. For the m cerns were defined [28,[30][31][32], resulting from a risk of bias ar process [31,32], and from a risk of bias in selection of the repo ever, for one study [29], the risk was even defined as high. A indicated that within the studies, three studies [29,31,32] con vitamin D (including those with a high risk of bias [29]), but it [28,30]. Table 5. The risk of bias assessments for studies, conducted using t tool for randomized trials, accompanied by the main results of the s review.

Ref
Overall Bias [28] [29] [30] [31] [32] -Low risk; -Some concerns -High risk; * the summar firming (if confirming a positive influence of vitamin D suppleme confirming (if not confirming a positive influence of vitamin D sup domains of risk of bias: D1-arising from the randomization proce the intended interventions; D3-due to missing outcome data; D4-D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available eviden the supplementation of vitamin D on mental health in adults eases obtained within randomized controlled trials (RCTs). not be considered as a strong confirmation of a general posi tation of vitamin D on mental health in adults with respira beneficial effect was observed for increased susceptibility t [29] and bronchial asthma [32], as well as for one study con for the other study conducted for COPD [28], and for pulmo beneficial effect was not observed. Not only should a gene concluded, but also a beneficial effect in specific conditions ca RCTs confirming were gathered for each mentioned disease ceptibility to respiratory tract infections, bronchial asthma a as a promising area to be studied in the future.
The effects observed for increased susceptibility to resp sociated with the general influence of vitamin D, being assoc [15]. It is observed that it influences the immunity by trigge cidin, being an antimicrobial peptide capable of mediating a the same time, vitamin D influences autophagy, as well as by promoting regulatory lymphocytes [34]. It was confirmed cerns were defined [28,[30][31][32], resulting from a process [31,32], and from a risk of bias in selecti ever, for one study [29], the risk was even defin indicated that within the studies, three studies [ vitamin D (including those with a high risk of it [28,30].

Discussion
This systematic review aimed to gather av the supplementation of vitamin D on mental he eases obtained within randomized controlled t not be considered as a strong confirmation of a tation of vitamin D on mental health in adult beneficial effect was observed for increased su [29] and bronchial asthma [32], as well as for o for the other study conducted for COPD [28], a beneficial effect was not observed. Not only s concluded, but also a beneficial effect in specific RCTs confirming were gathered for each menti ceptibility to respiratory tract infections, bronc as a promising area to be studied in the future.
The effects observed for increased suscept sociated with the general influence of vitamin D [15]. It is observed that it influences the immun cidin, being an antimicrobial peptide capable o the same time, vitamin D influences autophag by promoting regulatory lymphocytes [34]. It w The risk-of-bias assessments of-bias tool for randomized trials in the systematic review, are pre cerns were defined [28,[30][31][32], res process [31,32], and from a risk of ever, for one study [29], the risk indicated that within the studies, vitamin D (including those with it [28,30].

Discussion
This systematic review aime the supplementation of vitamin D eases obtained within randomize not be considered as a strong con tation of vitamin D on mental h beneficial effect was observed fo [29] and bronchial asthma [32], a for the other study conducted for beneficial effect was not observe concluded, but also a beneficial e RCTs confirming were gathered ceptibility to respiratory tract in as a promising area to be studied The effects observed for incr sociated with the general influen [15]. It is observed that it influen cidin, being an antimicrobial pep the same time, vitamin D influen by promoting regulatory lympho Confirming [30] Nutrients 2023, 15, x FOR PEER REVIEW 8 of 13 The risk-of-bias assessments for studies, conducted using the revised Cochrane riskof-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30].

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and The risk-of-bias assessments for studies, conducted using the revised Cochrane ris of-bias tool for randomized trials, accompanied by the main results of the studies includ in the systematic review, are presented in Table 5. For the majority of studies, some co cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomizati process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. Ho ever, for one study [29], the risk was even defined as high. At the same time, it should indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect vitamin D (including those with a high risk of bias [29]), but two studies did not confir it [28,30].

Discussion
This systematic review aimed to gather available evidence regarding the influence the supplementation of vitamin D on mental health in adults with respiratory system d eases obtained within randomized controlled trials (RCTs). However, the results shou not be considered as a strong confirmation of a general positive effect of the suppleme tation of vitamin D on mental health in adults with respiratory system diseases, as t beneficial effect was observed for increased susceptibility to respiratory tract infectio [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], wh for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such beneficial effect was not observed. Not only should a general positive influence not concluded, but also a beneficial effect in specific conditions cannot be stated, as only sing RCTs confirming were gathered for each mentioned disease. However, an increased su ceptibility to respiratory tract infections, bronchial asthma and COPD may be indicat as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are sociated with the general influence of vitamin D, being associated with immune functio [15]. It is observed that it influences the immunity by triggering the induction of cathe cidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. the same time, vitamin D influences autophagy, as well as adaptive immune respons by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review a The risk-of-bias assessments for studies, conducted using the revised of-bias tool for randomized trials, accompanied by the main results of the s in the systematic review, are presented in Table 5. For the majority of stu cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the process [31,32], and from a risk of bias in selection of the reported results [ ever, for one study [29], the risk was even defined as high. At the same ti indicated that within the studies, three studies [29,31,32] confirmed the be vitamin D (including those with a high risk of bias [29]), but two studies it [28,30].

Discussion
This systematic review aimed to gather available evidence regarding the supplementation of vitamin D on mental health in adults with respira eases obtained within randomized controlled trials (RCTs). However, th not be considered as a strong confirmation of a general positive effect of tation of vitamin D on mental health in adults with respiratory system beneficial effect was observed for increased susceptibility to respiratory [29] and bronchial asthma [32], as well as for one study conducted for CO for the other study conducted for COPD [28], and for pulmonary tubercul beneficial effect was not observed. Not only should a general positive i concluded, but also a beneficial effect in specific conditions cannot be state RCTs confirming were gathered for each mentioned disease. However, a ceptibility to respiratory tract infections, bronchial asthma and COPD m as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract i sociated with the general influence of vitamin D, being associated with im [15]. It is observed that it influences the immunity by triggering the indu cidin, being an antimicrobial peptide capable of mediating antimicrobial the same time, vitamin D influences autophagy, as well as adaptive imm by promoting regulatory lymphocytes [34]. It was confirmed by the system Nutrients 2023, 15, x FOR PEER REVIEW The risk-of-bias assessments for studies, conducted usin of-bias tool for randomized trials, accompanied by the main r in the systematic review, are presented in Table 5. For the m cerns were defined [28,[30][31][32], resulting from a risk of bias ar process [31,32], and from a risk of bias in selection of the repo ever, for one study [29], the risk was even defined as high. A indicated that within the studies, three studies [29,31,32] con vitamin D (including those with a high risk of bias [29]), but it [28,30].

Discussion
This systematic review aimed to gather available eviden the supplementation of vitamin D on mental health in adults eases obtained within randomized controlled trials (RCTs). not be considered as a strong confirmation of a general posi tation of vitamin D on mental health in adults with respira beneficial effect was observed for increased susceptibility t [29] and bronchial asthma [32], as well as for one study con for the other study conducted for COPD [28], and for pulmo beneficial effect was not observed. Not only should a gene concluded, but also a beneficial effect in specific conditions ca RCTs confirming were gathered for each mentioned disease ceptibility to respiratory tract infections, bronchial asthma a as a promising area to be studied in the future.
The effects observed for increased susceptibility to resp sociated with the general influence of vitamin D, being assoc [15]. It is observed that it influences the immunity by trigge cidin, being an antimicrobial peptide capable of mediating a the same time, vitamin D influences autophagy, as well as by promoting regulatory lymphocytes [34]. It was confirmed of-bias tool for randomized trials, accompanied in the systematic review, are presented in Tabl cerns were defined [28,[30][31][32], resulting from a process [31,32], and from a risk of bias in selecti ever, for one study [29], the risk was even defin indicated that within the studies, three studies [ vitamin D (including those with a high risk of it [28,30].

Discussion
This systematic review aimed to gather av the supplementation of vitamin D on mental he eases obtained within randomized controlled t not be considered as a strong confirmation of a tation of vitamin D on mental health in adult beneficial effect was observed for increased su [29] and bronchial asthma [32], as well as for o for the other study conducted for COPD [28], a beneficial effect was not observed. Not only s concluded, but also a beneficial effect in specific RCTs confirming were gathered for each menti ceptibility to respiratory tract infections, bronc as a promising area to be studied in the future.
The effects observed for increased suscept sociated with the general influence of vitamin D [15]. It is observed that it influences the immun cidin, being an antimicrobial peptide capable o the same time, vitamin D influences autophag by promoting regulatory lymphocytes [34]. It w of-bias tool for randomized trials, in the systematic review, are pre cerns were defined [28,[30][31][32], res process [31,32], and from a risk of ever, for one study [29], the risk w indicated that within the studies, vitamin D (including those with it [28,30].

Discussion
This systematic review aime the supplementation of vitamin D eases obtained within randomize not be considered as a strong con tation of vitamin D on mental h beneficial effect was observed fo [29] and bronchial asthma [32], a for the other study conducted for beneficial effect was not observe concluded, but also a beneficial ef RCTs confirming were gathered ceptibility to respiratory tract inf as a promising area to be studied The effects observed for incr sociated with the general influenc [15]. It is observed that it influen cidin, being an antimicrobial pep the same time, vitamin D influen by promoting regulatory lympho Not confirming [31] The risk-of-bias assessments for studies, conducted using the revised Cochrane riskof-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30]. Table 5. The risk of bias assessments for studies, conducted using the revised Cochrane risk-of-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review. -Some concerns -High risk; * the summary of conclusions defined as confirming (if confirming a positive influence of vitamin D supplementation on mental health) or not confirming (if not confirming a positive influence of vitamin D supplementation on mental health); domains of risk of bias: D1-arising from the randomization process; D2-due to deviations from the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcome; D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and The risk-of-bias assessments for studies, conducted using the revised Cochrane ris of-bias tool for randomized trials, accompanied by the main results of the studies includ in the systematic review, are presented in Table 5. For the majority of studies, some co cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomizati process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. Ho ever, for one study [29], the risk was even defined as high. At the same time, it should indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect vitamin D (including those with a high risk of bias [29]), but two studies did not confir it [28,30].

Discussion
This systematic review aimed to gather available evidence regarding the influence the supplementation of vitamin D on mental health in adults with respiratory system d eases obtained within randomized controlled trials (RCTs). However, the results shou not be considered as a strong confirmation of a general positive effect of the suppleme tation of vitamin D on mental health in adults with respiratory system diseases, as t beneficial effect was observed for increased susceptibility to respiratory tract infectio [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], wh for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such beneficial effect was not observed. Not only should a general positive influence not concluded, but also a beneficial effect in specific conditions cannot be stated, as only sing RCTs confirming were gathered for each mentioned disease. However, an increased su ceptibility to respiratory tract infections, bronchial asthma and COPD may be indicat as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are sociated with the general influence of vitamin D, being associated with immune functio [15]. It is observed that it influences the immunity by triggering the induction of cathe cidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. the same time, vitamin D influences autophagy, as well as adaptive immune respons by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review a Nutrients 2023, 15, x FOR PEER REVIEW The risk-of-bias assessments for studies, conducted using the revised of-bias tool for randomized trials, accompanied by the main results of the s in the systematic review, are presented in Table 5. For the majority of stu cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the process [31,32], and from a risk of bias in selection of the reported results [ ever, for one study [29], the risk was even defined as high. At the same ti indicated that within the studies, three studies [29,31,32] confirmed the be vitamin D (including those with a high risk of bias [29]), but two studies it [28,30].

Discussion
This systematic review aimed to gather available evidence regarding the supplementation of vitamin D on mental health in adults with respira eases obtained within randomized controlled trials (RCTs). However, th not be considered as a strong confirmation of a general positive effect of tation of vitamin D on mental health in adults with respiratory system beneficial effect was observed for increased susceptibility to respiratory [29] and bronchial asthma [32], as well as for one study conducted for CO for the other study conducted for COPD [28], and for pulmonary tubercul beneficial effect was not observed. Not only should a general positive i concluded, but also a beneficial effect in specific conditions cannot be state RCTs confirming were gathered for each mentioned disease. However, a ceptibility to respiratory tract infections, bronchial asthma and COPD m as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract i sociated with the general influence of vitamin D, being associated with im [15]. It is observed that it influences the immunity by triggering the indu cidin, being an antimicrobial peptide capable of mediating antimicrobial the same time, vitamin D influences autophagy, as well as adaptive imm by promoting regulatory lymphocytes [34]. It was confirmed by the system Nutrients 2023, 15, x FOR PEER REVIEW The risk-of-bias assessments for studies, conducted usin of-bias tool for randomized trials, accompanied by the main r in the systematic review, are presented in Table 5. For the m cerns were defined [28,[30][31][32], resulting from a risk of bias ar process [31,32], and from a risk of bias in selection of the repo ever, for one study [29], the risk was even defined as high. A indicated that within the studies, three studies [29,31,32] con vitamin D (including those with a high risk of bias [29]), but it [28,30].

Discussion
This systematic review aimed to gather available eviden the supplementation of vitamin D on mental health in adults eases obtained within randomized controlled trials (RCTs). not be considered as a strong confirmation of a general posi tation of vitamin D on mental health in adults with respira beneficial effect was observed for increased susceptibility t [29] and bronchial asthma [32], as well as for one study con for the other study conducted for COPD [28], and for pulmo beneficial effect was not observed. Not only should a gene concluded, but also a beneficial effect in specific conditions ca RCTs confirming were gathered for each mentioned disease ceptibility to respiratory tract infections, bronchial asthma a as a promising area to be studied in the future.
The effects observed for increased susceptibility to resp sociated with the general influence of vitamin D, being assoc [15]. It is observed that it influences the immunity by trigge cidin, being an antimicrobial peptide capable of mediating a the same time, vitamin D influences autophagy, as well as by promoting regulatory lymphocytes [34]. It was confirmed The risk-of-bias assessments for studies, co of-bias tool for randomized trials, accompanied in the systematic review, are presented in Tabl cerns were defined [28,[30][31][32], resulting from a process [31,32], and from a risk of bias in selecti ever, for one study [29], the risk was even defin indicated that within the studies, three studies [ vitamin D (including those with a high risk of it [28,30]. [32] -Low risk; -Some concerns -High risk firming (if confirming a positive influence of vitami confirming (if not confirming a positive influence of domains of risk of bias: D1-arising from the rando the intended interventions; D3-due to missing outc D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather av the supplementation of vitamin D on mental he eases obtained within randomized controlled t not be considered as a strong confirmation of a tation of vitamin D on mental health in adult beneficial effect was observed for increased su [29] and bronchial asthma [32], as well as for o for the other study conducted for COPD [28], a beneficial effect was not observed. Not only s concluded, but also a beneficial effect in specific RCTs confirming were gathered for each menti ceptibility to respiratory tract infections, bronc as a promising area to be studied in the future.
The effects observed for increased suscept sociated with the general influence of vitamin D [15]. It is observed that it influences the immun cidin, being an antimicrobial peptide capable o the same time, vitamin D influences autophag by promoting regulatory lymphocytes [34]. It w The risk-of-bias assessments of-bias tool for randomized trials, in the systematic review, are pre cerns were defined [28,[30][31][32], res process [31,32], and from a risk of ever, for one study [29], the risk w indicated that within the studies, vitamin D (including those with it [28,30]. Table 5. The risk of bias assessments tool for randomized trials, accompan review.

Discussion
This systematic review aime the supplementation of vitamin D eases obtained within randomize not be considered as a strong con tation of vitamin D on mental h beneficial effect was observed fo [29] and bronchial asthma [32], a for the other study conducted for beneficial effect was not observe concluded, but also a beneficial ef RCTs confirming were gathered ceptibility to respiratory tract inf as a promising area to be studied The effects observed for incr sociated with the general influenc [15]. It is observed that it influen cidin, being an antimicrobial pep the same time, vitamin D influen by promoting regulatory lympho Confirming [32] The risk-of-bias assessments for studies, conducted using the revised Cochrane riskof-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30]. Table 5. The risk of bias assessments for studies, conducted using the revised Cochrane risk-of-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review. -Some concerns -High risk; * the summary of conclusions defined as confirming (if confirming a positive influence of vitamin D supplementation on mental health) or not confirming (if not confirming a positive influence of vitamin D supplementation on mental health); domains of risk of bias: D1-arising from the randomization process; D2-due to deviations from the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcome; D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and The risk-of-bias assessments for studies, conducted using the revised Cochrane ris of-bias tool for randomized trials, accompanied by the main results of the studies includ in the systematic review, are presented in Table 5. For the majority of studies, some co cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomizati process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. Ho ever, for one study [29], the risk was even defined as high. At the same time, it should indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect vitamin D (including those with a high risk of bias [29]), but two studies did not confir it [28,30]. Table 5. The risk of bias assessments for studies, conducted using the revised Cochrane risk-of-b tool for randomized trials, accompanied by the main results of the studies included in the systema review. -Some concerns -High risk; * the summary of conclusions defined as co firming (if confirming a positive influence of vitamin D supplementation on mental health) or n confirming (if not confirming a positive influence of vitamin D supplementation on mental healt domains of risk of bias: D1-arising from the randomization process; D2-due to deviations fro the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcom D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence the supplementation of vitamin D on mental health in adults with respiratory system d eases obtained within randomized controlled trials (RCTs). However, the results shou not be considered as a strong confirmation of a general positive effect of the suppleme tation of vitamin D on mental health in adults with respiratory system diseases, as t beneficial effect was observed for increased susceptibility to respiratory tract infectio [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], wh for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such beneficial effect was not observed. Not only should a general positive influence not concluded, but also a beneficial effect in specific conditions cannot be stated, as only sing RCTs confirming were gathered for each mentioned disease. However, an increased su ceptibility to respiratory tract infections, bronchial asthma and COPD may be indicat as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are sociated with the general influence of vitamin D, being associated with immune functio [15]. It is observed that it influences the immunity by triggering the induction of cathe cidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. the same time, vitamin D influences autophagy, as well as adaptive immune respons by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review a The risk-of-bias assessments for studies, conducted using the revised of-bias tool for randomized trials, accompanied by the main results of the s in the systematic review, are presented in Table 5. For the majority of stu cerns were defined [28,[30][31][32], resulting from a risk of bias arising from the process [31,32], and from a risk of bias in selection of the reported results [ ever, for one study [29], the risk was even defined as high. At the same ti indicated that within the studies, three studies [29,31,32] confirmed the be vitamin D (including those with a high risk of bias [29]), but two studies it [28,30].

Discussion
This systematic review aimed to gather available evidence regarding the supplementation of vitamin D on mental health in adults with respira eases obtained within randomized controlled trials (RCTs). However, th not be considered as a strong confirmation of a general positive effect of tation of vitamin D on mental health in adults with respiratory system beneficial effect was observed for increased susceptibility to respiratory [29] and bronchial asthma [32], as well as for one study conducted for CO for the other study conducted for COPD [28], and for pulmonary tubercul beneficial effect was not observed. Not only should a general positive i concluded, but also a beneficial effect in specific conditions cannot be state RCTs confirming were gathered for each mentioned disease. However, a ceptibility to respiratory tract infections, bronchial asthma and COPD m as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract i sociated with the general influence of vitamin D, being associated with im [15]. It is observed that it influences the immunity by triggering the indu cidin, being an antimicrobial peptide capable of mediating antimicrobial the same time, vitamin D influences autophagy, as well as adaptive imm by promoting regulatory lymphocytes [34]. It was confirmed by the system The risk-of-bias assessments for studies, conducted usin of-bias tool for randomized trials, accompanied by the main r in the systematic review, are presented in Table 5. For the m cerns were defined [28,[30][31][32], resulting from a risk of bias ar process [31,32], and from a risk of bias in selection of the repo ever, for one study [29], the risk was even defined as high. A indicated that within the studies, three studies [29,31,32] con vitamin D (including those with a high risk of bias [29]), but it [28,30].

Discussion
This systematic review aimed to gather available eviden the supplementation of vitamin D on mental health in adults eases obtained within randomized controlled trials (RCTs). not be considered as a strong confirmation of a general posi tation of vitamin D on mental health in adults with respira beneficial effect was observed for increased susceptibility t [29] and bronchial asthma [32], as well as for one study con for the other study conducted for COPD [28], and for pulmo beneficial effect was not observed. Not only should a gene concluded, but also a beneficial effect in specific conditions ca RCTs confirming were gathered for each mentioned disease ceptibility to respiratory tract infections, bronchial asthma a as a promising area to be studied in the future.
The effects observed for increased susceptibility to resp sociated with the general influence of vitamin D, being assoc [15]. It is observed that it influences the immunity by trigge cidin, being an antimicrobial peptide capable of mediating a the same time, vitamin D influences autophagy, as well as by promoting regulatory lymphocytes [34]. It was confirmed The risk-of-bias assessments for studies, co of-bias tool for randomized trials, accompanied in the systematic review, are presented in Tabl cerns were defined [28,[30][31][32], resulting from a process [31,32], and from a risk of bias in selecti ever, for one study [29], the risk was even defin indicated that within the studies, three studies [ vitamin D (including those with a high risk of it [28,30].

Discussion
This systematic review aimed to gather av the supplementation of vitamin D on mental he eases obtained within randomized controlled t not be considered as a strong confirmation of a tation of vitamin D on mental health in adult beneficial effect was observed for increased su [29] and bronchial asthma [32], as well as for o for the other study conducted for COPD [28], a beneficial effect was not observed. Not only s concluded, but also a beneficial effect in specific RCTs confirming were gathered for each menti ceptibility to respiratory tract infections, bronc as a promising area to be studied in the future.
The effects observed for increased suscept sociated with the general influence of vitamin D [15]. It is observed that it influences the immun cidin, being an antimicrobial peptide capable o the same time, vitamin D influences autophag by promoting regulatory lymphocytes [34]. It w The risk-of-bias assessments of-bias tool for randomized trials, in the systematic review, are pre cerns were defined [28,[30][31][32], res process [31,32], and from a risk of ever, for one study [29], the risk w indicated that within the studies, vitamin D (including those with it [28,30].

Discussion
This systematic review aime the supplementation of vitamin D eases obtained within randomize not be considered as a strong con tation of vitamin D on mental h beneficial effect was observed fo [29] and bronchial asthma [32], a for the other study conducted for beneficial effect was not observe concluded, but also a beneficial ef RCTs confirming were gathered ceptibility to respiratory tract inf as a promising area to be studied The effects observed for incr sociated with the general influenc [15]. It is observed that it influen cidin, being an antimicrobial pep the same time, vitamin D influen by promoting regulatory lympho The risk-of-bias assessments for studies, conducted using the revised Cochrane riskof-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30]. -Some concerns -High risk; * the summary of conclusions defined as confirming (if confirming a positive influence of vitamin D supplementation on mental health) or not confirming (if not confirming a positive influence of vitamin D supplementation on mental health); domains of risk of bias: D1-arising from the randomization process; D2-due to deviations from the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcome; D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and -Low risk; Nutrients 2023, 15, x FOR PEER REVIEW 8 of 13 The risk-of-bias assessments for studies, conducted using the revised Cochrane riskof-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30]. -Some concerns -High risk; * the summary of conclusions defined as confirming (if confirming a positive influence of vitamin D supplementation on mental health) or not confirming (if not confirming a positive influence of vitamin D supplementation on mental health); domains of risk of bias: D1-arising from the randomization process; D2-due to deviations from the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcome; D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and -Some concerns The risk-of-bias assessments for studies, conducted using the revised Cochrane riskof-bias tool for randomized trials, accompanied by the main results of the studies included in the systematic review, are presented in Table 5. For the majority of studies, some concerns were defined [28,[30][31][32], resulting from a risk of bias arising from the randomization process [31,32], and from a risk of bias in selection of the reported results [28,[30][31][32]. However, for one study [29], the risk was even defined as high. At the same time, it should be indicated that within the studies, three studies [29,31,32] confirmed the beneficial effect of vitamin D (including those with a high risk of bias [29]), but two studies did not confirm it [28,30]. -Some concerns -High risk; * the summary of conclusions defined as confirming (if confirming a positive influence of vitamin D supplementation on mental health) or not confirming (if not confirming a positive influence of vitamin D supplementation on mental health); domains of risk of bias: D1-arising from the randomization process; D2-due to deviations from the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcome; D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and -High risk; * the summary of conclusions defined as confirming (if confirming a positive influence of vitamin D supplementation on mental health) or not confirming (if not confirming a positive influence of vitamin D supplementation on mental health); domains of risk of bias: D1-arising from the randomization process; D2-due to deviations from the intended interventions; D3-due to missing outcome data; D4-in measurement of the outcome; D5-in the selection of the reported results.

Discussion
This systematic review aimed to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). However, the results should not be considered as a strong confirmation of a general positive effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases, as the beneficial effect was observed for increased susceptibility to respiratory tract infections [29] and bronchial asthma [32], as well as for one study conducted for COPD [31], while for the other study conducted for COPD [28], and for pulmonary tuberculosis [30], such a beneficial effect was not observed. Not only should a general positive influence not be concluded, but also a beneficial effect in specific conditions cannot be stated, as only single RCTs confirming were gathered for each mentioned disease. However, an increased susceptibility to respiratory tract infections, bronchial asthma and COPD may be indicated as a promising area to be studied in the future.
The effects observed for increased susceptibility to respiratory tract infections are associated with the general influence of vitamin D, being associated with immune functions [15]. It is observed that it influences the immunity by triggering the induction of cathelicidin, being an antimicrobial peptide capable of mediating antimicrobial activity [33]. At the same time, vitamin D influences autophagy, as well as adaptive immune responses, by promoting regulatory lymphocytes [34]. It was confirmed by the systematic review and meta-analysis of RCTs by Bergman et al. [35], which indicated that vitamin D has a protective effect against respiratory tract infections. At the same time, the systematic review by Charan et al. [36] indicated that it may be even more observable in children than in adults. Some similar observations were formulated for hospital-acquired infections, including inter alia wound infections and sepsis [37], but vitamin D failed to be effective against respiratory infections after lung transplants [38]. During the COVID-19 pandemic, numerous studies also verified the effectiveness of vitamin D in the prevention and treatment of COVID-19 infection. Within the systematic review by Jordan et al. [39], it was concluded that its supplementation may play an important role in protecting from acute infections, and in the treatment of high-risk individuals, it may prevent progression to a Nutrients 2023, 15, 971 9 of 12 critical clinical condition, and as a result, it may reduce mortality. Taking this into account, the supplementation of vitamin D is concluded to be safe option to prevent against acute respiratory tract infections [40].
For the effect of vitamin D on bronchial asthma, some conflicting data were obtained from clinical trials, but it is emphasized that vitamin D deficiency may influence the inflammatory response in the airways [41]. However, the effect of supplementation is not always observed [42]. Positive conclusions were formulated within a RCT by Arshi et al. [43], as they proved that the supplementation of vitamin D in patients, including adults and adolescents with mild to moderate persistent asthma, significantly improved forced expiratory volume in 1 s (FEV1). It is generally associated with low vitamin D levels in asthmatic patients, which may be improved during supplementation, and as a result, it may enhance asthma control [44], as the vitamin D status in asthmatic patients is associated with their lung function [45]. However, other studies did not provide such positive observations, as in children with mild asthma, no effect of supplementation of vitamin D on airway reactivity and inflammation was stated [46]. Taking this into account, it is indicated that there is some potential to use vitamin D in the prevention and treatment of asthma [47].
For COPD, similarly to respiratory tract infections and asthma, there are some beneficial observations. The RCT by Khan et al. [48] indicated that the supplementation of vitamin D in COPD patients may be effective in reducing the number of acute exacerbations. At the same time, the systematic review and meta-analysis by Zhu et al. [49] indicated that vitamin D status is inversely associated with the risk and severity of COPD, as well as with its exacerbations. Similarly, the systematic review and meta-analysis of individual participant data from RCTs by Jolliffe et al. [50] indicated that the supplementation of vitamin D may effectively reduce the rate of COPD exacerbations in patients with low baseline vitamin D levels, but not in those with higher ones. Taking this into account, the routine control of vitamin D status is suggested to be undertaken in COPD patients [51].
The results of the studies described above confirm or at least suggest the positive role of vitamin D in respiratory functions. At the same time, the beneficial role of vitamin D in mental health in the general population is known, which was observed mainly for depression [52][53][54], but also for the occurrence of negative emotions [55], and for quality of life [56]. The mechanism of the influence of vitamin D on mental health is associated with the fact that vitamin D may cross the blood-brain barrier, which results in the activation of receptors in brain cells and a direct impact in the central nervous system [57]. At the same time, it is suggested that vitamin D and Vitamin D receptors (VDRs) may influence the regulation of human behavior, as VDRs are present in the cortex, cerebellum, and limbic system of the brain [58]. Notwithstanding this, the mechanism is not simple, due to the fact that VDR genes are polymorphic with frequent variations, causing vitamin-D-related dysfunctions [59].
However, the question about the potential effect of vitamin D on mental health in patients with respiratory system diseases is still unanswered. At the same time, concurrent diseases and other disorders may interfere, as they may be also associated with the role of vitamin D, as indicated for obesity [60], or even the common cold [61]. In spite of the fact that the number of studies conducted for patients with respiratory system diseases indicated some positive observations, it was not sufficient to formulate explicit conclusions.

Conclusions
Taking into account the evidence gathered, in spite of a positive influence of vitamin D on mental health in individuals with an increased susceptibility to respiratory tract infections and bronchial asthma, the conducted systematic review is not a strong confirmation of the beneficial effect of supplementation of vitamin D on mental health in adults with respiratory system diseases.